tbuckley/cabot-search huggingface dataset:
The role and prospect of lysine‐specific demethylases in cancer chemoresistance
Authors: Ying‐Qi Song, Guan‐Jun Yang, Dik‐Lung Ma, Wanhe Wang, Chung‐Hang Leung
Journal: Medicinal Research Reviews (2023)

Histone methylation plays a key function in modulating gene expression, and preserving genome integrity and epigenetic inheritance. However, aberrations of histone methylation are commonly observed in human diseases, especially cancer. Lysine methylation mediated by histone methyltransferases can be reversed by lysine demethylases (KDMs), which remove methyl marks from histone lysine residues. Currently, drug resistance is a main impediment for cancer therapy. KDMs have been found to mediate drug tolerance of many cancers via altering the metabolic profile of cancer cells, upregulating the ratio of cancer stem cells and drug-tolerant genes, and promoting the epithelial-mesenchymal transition and metastatic ability. Moreover, different cancers show distinct oncogenic addictions for KDMs. The abnormal activation or overexpression of KDMs can alter gene expression signatures to enhance cell survival and drug resistance in cancer cells. In this review, we describe the structural features and functions of KDMs, the KDMs preferences of different cancers, and the mechanisms of drug resistance resulting from KDMs. We then survey KDM inhibitors that have been used for combating drug resistance in cancer, and discuss the opportunities and challenges of KDMs as therapeutic targets for cancer drug resistance.
In older adults with hypertension, chlorthalidone vs. hydrochlorothiazide did not reduce major CV events or deaths at 2.4 y
Authors: Chirag Bavishi
Journal: Annals of Internal Medicine (2023)

Source Citation Diuretic Comparison Project Writing Group; Ishani A, Cushman WC, Leatherman SM, et al. Chlorthalidone vs. hydrochlorothiazide for hypertension–cardiovascular events. N Engl J Med. 2022;387:2401-10. 36516076
Mindfulness Training and Exercise and Cognitive Function in Older Adults
Authors: Elena Salmoirago-Blotcher, Ronald Cohen
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in<i>FLT3</i>-Mutant Leukemia
Authors: Marie Sabatier, Rudy Birsen, Laura Lauture, Sarah Mouche, Paolo Angelino, Jonas Dehairs, Léa Goupille, Ismael Boussaid, Maël Heiblig, Emeline Boet, Ambrine Sahal, Estelle Saland, Juliana C. Santos, Marc Armengol, Miranda Fernández-Serrano, Thomas Farge, Guillaume Cognet, Federico Simonetta, Corentin Pignon, Antoine Graffeuil, Céline Mazzotti, Hervé Avet-Loiseau, Océane Delos, Justine Bertrand-Michel, Amélie Chedru, Vilma Dembitz, Paolo Gallipoli, Natasha S. Anstee, Sun Loo, Andrew H. Wei, Martin Carroll, Armelle Goubard, Rémy Castellano, Yves Collette, François Vergez, Véronique Mansat-De Mas, Sarah Bertoli, Suzanne Tavitian, Muriel Picard, Christian Récher, Nathalie Bourges-Abella, Fanny Granat, Olivier Kosmider, Pierre Sujobert, Benoit Colsch, Carine Joffre, Lucille Stuani, Johannes V. Swinnen, Hervé Guillou, Gael Roué, Nawad Hakim, Anne S. Dejean, Petros Tsantoulis, Clément Larrue, Didier Bouscary, Jerome Tamburini, Jean-Emmanuel Sarry
Journal: Cancer Discovery (2023)

Abstract Although transcription factor CCAAT-enhancer binding protein α (C/EBPα) is critical for normal and leukemic differentiation, its role in cell and metabolic homeostasis is largely unknown in cancer. Here, multiomics analyses uncovered a coordinated activation of C/EBPα and Fms-like tyrosine kinase 3 (FLT3) that increased lipid anabolism in vivo and in patients with FLT3-mutant acute myeloid leukemia (AML). Mechanistically, C/EBPα regulated the fatty acid synthase (FASN)–stearoyl-CoA desaturase (SCD) axis to promote fatty acid (FA) biosynthesis and desaturation. We further demonstrated that FLT3 or C/EBPα inactivation decreased monounsaturated FA incorporation to membrane phospholipids through SCD downregulation. Consequently, SCD inhibition enhanced susceptibility to lipid redox stress that was exploited by combining FLT3 and glutathione peroxidase 4 inhibition to trigger lipid oxidative stress, enhancing ferroptotic death of FLT3-mutant AML cells. Altogether, our study reveals a C/EBPα function in lipid homeostasis and adaptation to redox stress, and a previously unreported vulnerability of FLT3-mutant AML to ferroptosis with promising therapeutic application. Significance: FLT3 mutations are found in 30% of AML cases and are actionable by tyrosine kinase inhibitors. Here, we discovered that C/EBPα regulates FA biosynthesis and protection from lipid redox stress downstream mutant-FLT3 signaling, which confers a vulnerability to ferroptosis upon FLT3 inhibition with therapeutic potential in AML. This article is highlighted in the In This Issue feature, p. 1501
Pigs or Pumps: A new strategy emerges for liver perfusion
Authors: Jacqueline I. Kim, Alejandro Torres-Hernandez, Adam Griesemer
Journal: Hepatology (2023)

1Transplant Institute, NYU Langone Health, New York, NY 2403 East 34th Street, Room 313, New York, NY 10016 List of Abbreviations: None Financial Support: None ("Xenogeneic cross-circulation for physiologic support and recovery of ex vivo human livers") Correspondence Adam Griesemer MD, 403 East 34th Street, Room 313, New York, NY 10016. Email: [email protected]
Core outcome sets, developed collaboratively with patients, can improve the relevance and comparability of clinical trials
Authors: Alexander G. Mathioudakis, Ekaterina Khaleva, Markus Fally, Paula R. Williamson, Jens-Ulrik Jensen, Tim W. Felton, Chris Brightling, Andrew Bush, Tonya Winders, John Linnell, Valeria Ramiconi, Courtney Coleman, Tobias Welte, Graham Roberts, Jørgen Vestbo
Journal: European Respiratory Journal (2023)

<b>#RCTs in #Respiratory medicine require harmonisation. A core outcome set #COS is an agreed minimum set of outcomes that are critical for decision-making and should be evaluated in all future clinical trials.</b> https://bit.ly/3XQmbtH
Errors in Results and Tables
Journal: JAMA Internal Medicine (2023)

Errors in Table 1, eTable 1, and Figure 2: The Original Investigation titled, "Coffee Consumption and Incident Tachyarrhythmias: Reported Behavior, Mendelian Randomization, and Their Interactions," 1 published in the September 2021 issue, included data errors that appeared in Table 1 and eTable 1, as well some missing explanatory text in the caption of Figure 2.These errors did not affect the results of the study.
Neural dynamics underlying associative learning in the dorsal and ventral hippocampus
Authors: Jeremy S. Biane, Max A. Ladow, Fabio Stefanini, Sayi P. Boddu, Austin Fan, Shazreh Hassan, Naz Dundar, Daniel L. Apodaca-Montano, Lexi Zichen Zhou, Varya Fayner, Nicholas I. Woods, Mazen A. Kheirbek
Journal: Nature Neuroscience (2023)
Unstructured Reading: Some Thoughts on Browsing
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Triglyceride cycling enables modification of stored fatty acids
Authors: Klaus Wunderling, Jelena Zurkovic, Fabian Zink, Lars Kuerschner, Christoph Thiele
Journal: Nature Metabolism (2023)

Triglyceride cycling is the process of continuous degradation and re-synthesis of triglyceride in cellular stores. We show in 3T3-L1 adipocytes that triglycerides are subject to rapid turnover and re-arrangement of fatty acids with an estimated half-life of 2-4 h. We develop a tracing technology that can simultaneously and quantitatively follow the metabolism of multiple fatty acids to study the triglyceride futile substrate cycle directly and with molecular species resolution. Our approach is based on alkyne fatty acid tracers and mass spectrometry. The triglyceride cycling is connected to modification of released fatty acids by elongation and desaturation. Through cycling and modification, saturated fatty acids are slowly converted to monounsaturated fatty acids, and linoleic acid to arachidonic acid. We conclude that triglyceride cycling renders stored fatty acids accessible for metabolic alteration. The overall process facilitates cellular adjustments to the stored fatty acid pool to meet changing needs of the cell.
<i>KIT</i> and <i>PDGFRA</i> Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial
Authors: Heikki Joensuu, Eva Wardelmann, Mikael Eriksson, Annette Reichardt, Kirsten Sundby Hall, Jochen Schütte, Silke Cameron, Peter Hohenberger, Harri Sihto, Philipp J. Jost, Lars H. Lindner, Sebastian Bauer, Bengt Nilsson, Raija Kallio, Tommi Pesonen, Peter Reichardt
Journal: Clinical Cancer Research (2023)

Limited data are available about the influence of KIT and PDGFRA mutations on overall survival (OS) of patients with gastrointestinal stromal tumor (GIST) treated with adjuvant imatinib.The Scandinavian Sarcoma Group XVIII/AIO multicenter trial accrued 400 patients with a high risk for GIST recurrence after macroscopically complete surgery between February 4, 2004, and September 29, 2008. The patients received adjuvant imatinib 400 mg/day for either 1 year or 3 years based on random allocation. We analyzed using conventional sequencing KIT and PDGFRA mutations centrally from 341 (85%) patients who had localized, centrally confirmed GIST, and correlated the results with recurrence-free survival (RFS) and OS in exploratory analyses.During a median follow-up time of 10 years, 164 RFS events and 76 deaths occurred. Most patients were re-treated with imatinib when GIST recurred. Patients with KIT exon 11 deletion or indel mutation treated with 3 years of adjuvant imatinib survived longer than patients treated for 1 year [10-year OS 86% versus 64%, respectively; HR, 0.34; 95% confidence interval (CI), 0.15-0.72; P = 0.007], and also had longer RFS (10-year RFS 47% versus 29%; HR, 0.48; 95% CI, 0.31-0.74; P < 0.001). Patients with KIT exon 9 mutation had unfavorable OS regardless of the duration of adjuvant imatinib.Compared with 1 year of imatinib, 3 years of adjuvant imatinib led to 66% reduction in the estimated risk of death and a high 10-year OS rate in the subset of patients with a KIT exon 11 deletion/indel mutation.
3D Printing of Extracellular Matrix‐Based Multicomponent, All‐Natural, Highly Elastic, and Functional Materials toward Vascular Tissue Engineering
Authors: Melis Isik, Ece Karakaya, Tugba Sezgin Arslan, Deniz Atila, Yasar Kemal Erdogan, Yavuz Emre Arslan, Hakan Eskizengin, Cemil Can Eylem, Emirhan Nemutlu, Batur Ercan, Matteo D'Este, Babatunde O. Okesola, Burak Derkus
Journal: Advanced Healthcare Materials (2023)

3D printing offers an exciting opportunity to fabricate biological constructs with specific geometries, clinically relevant sizes, and functions for biomedical applications. However, successful application of 3D printing is limited by the narrow range of printable and bio-instructive materials. Multicomponent hydrogel bioinks present unique opportunities to create bio-instructive materials able to display high structural fidelity and fulfill the mechanical and functional requirements for in situ tissue engineering. Herein, 3D printable and perfusable multicomponent hydrogel constructs with high elasticity, self-recovery properties, excellent hydrodynamic performance, and improved bioactivity are reported. The materials' design strategy integrates fast gelation kinetics of sodium alginate (Alg), in situ crosslinking of tyramine-modified hyaluronic acid (HAT), and temperature-dependent self-assembly and biological functions of decellularized aorta (dAECM). Using extrusion-based printing approach, the capability to print the multicomponent hydrogel bioinks with high precision into a well-defined vascular constructs able to withstand flow and repetitive cyclic compressive loading, is demonstrated. Both in vitro and pre-clinical models are used to show the pro-angiogenic and anti-inflammatory properties of the multicomponent vascular constructs. This study presents a strategy to create new bioink whose functional properties are greater than the sum of their components and with potential applications in vascular tissue engineering and regenerative medicine.
Differences in Treatment Patterns and Outcomes of Acute Myocardial Infarction for Low- and High-Income Patients in 6 Countries
Authors: Bruce E. Landon, Laura A. Hatfield, Pieter Bakx, Amitava Banerjee, Yu-Chin Chen, Christina Fu, Michal Gordon, Renaud Heine, Nicole Huang, Dennis T. Ko, Lisa M. Lix, Victor Novack, Laura Pasea, Feng Qiu, Therese A. Stukel, Carin Uyl-de Groot, Lin Yan, Gabe Weinreb, Peter Cram
Journal: JAMA (2023)

Differences in the organization and financing of health systems may produce more or less equitable outcomes for advantaged vs disadvantaged populations. We compared treatments and outcomes of older high- and low-income patients across 6 countries.To determine whether treatment patterns and outcomes for patients presenting with acute myocardial infarction differ for low- vs high-income individuals across 6 countries.Serial cross-sectional cohort study of all adults aged 66 years or older hospitalized with acute myocardial infarction from 2013 through 2018 in the US, Canada, England, the Netherlands, Taiwan, and Israel using population-representative administrative data.Being in the top and bottom quintile of income within and across countries.Thirty-day and 1-year mortality; secondary outcomes included rates of cardiac catheterization and revascularization, length of stay, and readmission rates.We studied 289 376 patients hospitalized with ST-segment elevation myocardial infarction (STEMI) and 843 046 hospitalized with non-STEMI (NSTEMI). Adjusted 30-day mortality generally was 1 to 3 percentage points lower for high-income patients. For instance, 30-day mortality among patients admitted with STEMI in the Netherlands was 10.2% for those with high income vs 13.1% for those with low income (difference, -2.8 percentage points [95% CI, -4.1 to -1.5]). One-year mortality differences for STEMI were even larger than 30-day mortality, with the highest difference in Israel (16.2% vs 25.3%; difference, -9.1 percentage points [95% CI, -16.7 to -1.6]). In all countries, rates of cardiac catheterization and percutaneous coronary intervention were higher among high- vs low-income populations, with absolute differences ranging from 1 to 6 percentage points (eg, 73.6% vs 67.4%; difference, 6.1 percentage points [95% CI, 1.2 to 11.0] for percutaneous intervention in England for STEMI). Rates of coronary artery bypass graft surgery for patients with STEMI in low- vs high-income strata were similar but for NSTEMI were generally 1 to 2 percentage points higher among high-income patients (eg, 12.5% vs 11.0% in the US; difference, 1.5 percentage points [95% CI, 1.3 to 1.8 ]). Thirty-day readmission rates generally also were 1 to 3 percentage points lower and hospital length of stay generally was 0.2 to 0.5 days shorter for high-income patients.High-income individuals had substantially better survival and were more likely to receive lifesaving revascularization and had shorter hospital lengths of stay and fewer readmissions across almost all countries. Our results suggest that income-based disparities were present even in countries with universal health insurance and robust social safety net systems.
Publisher Correction: Immune landscape in invasive ductal and lobular breast cancer reveals a divergent macrophage-driven microenvironment
Authors: Sayali Onkar, Jian Cui, Jian Zou, Carly Cardello, Anthony R. Cillo, Mostofa Rafid Uddin, April Sagan, Marion Joy, Hatice U. Osmanbeyoglu, Katherine L. Pogue-Geile, Priscilla F. McAuliffe, Peter C. Lucas, George C. Tseng, Adrian V. Lee, Tullia C. Bruno, Steffi Oesterreich, Dario A. A. Vignali
Journal: Nature Cancer (2023)
The snapdragon genomes reveal the evolutionary dynamics of the <i>S</i> locus supergene
Authors: Sihui Zhu, Yu’e Zhang, Lucy Copsy, Qianqian Han, Dongfeng Zheng, Enrico Coen, Yongbiao Xue
Journal: Molecular Biology and Evolution (2023)

The genus Antirrhinum has been used as a model to study self-incompatibility extensively. The multi-allelic S-locus, carrying a pistil S-RNase and dozens of S-locus F-box (SLF) genes, underlies the genetic control of self-incompatibility (SI) in Antirrhinum hispanicum. However, there have been limited studies on the genomic organization of the S-locus supergene due to a lack of high-quality genomic data. Here, we present the chromosome-level reference and haplotype-resolved genome assemblies of a self-incompatible A. hispanicum line, AhS7S8. For the first time, 2 complete A. hispanicum S-haplotypes spanning ∼1.2 Mb and containing a total of 32 SLFs were reconstructed, whereas most of the SLFs derived from retroelement-mediated proximal or tandem duplication ∼122 Mya. Back then, the S-RNase gene and incipient SLFs came into linkage to form the pro-type of type-1 S-locus in the common ancestor of eudicots. Furthermore, we detected a pleiotropic cis-transcription factor (TF) associated with regulating the expression of SLFs, and two miRNAs may control the expression of this TF. Interspecific S-locus and intraspecific S-haplotype comparisons revealed the dynamic nature and polymorphism of the S-locus supergene mediated by continuous gene duplication, segmental translocation or loss, and TE-mediated transposition events. Our data provide an excellent resource for future research on the evolutionary studies of the S-RNase-based self-incompatibility system.
BMA delays ballot on consultant strike, as government talks continue
Authors: Elisabeth Mahase
Journal: BMJ (2023)

The BMA has postponed its strike ballot for consultants in England, pushing it back almost a month, from 17 April to 15 May, after it held early but "constructive talks" with the government.In February more than 17 000 consultants in England voted for strike action over pensions and pay in a consultative ballot, which does not provide a legal mandate.The turnout was 61%, and 86% voted in favour of industrial action. 1 A second, legal, ballot was then planned for this month, but after talks with the government that led to "significant changes to pension taxation" 2 and a commitment from the health and social care secretary for England, Steve Barclay, for "meaningful talks" on pay, the union has decided to hold off on launching it."While these talks are still at an early stage, the BMA has agreed to pause launching the ballot to allow the talks to take place," the announcement said.It added that the delay gave the Department for Health and Social Care "ample time" to engage with the BMA and "work towards an offer that will reverse the erosion of consultant pay and restore the pay review body (DDRB) to its original purpose and independence."If the government did not meet these demands, the formal strike ballot would be launched, the BMA said.Vishal Sharma, chair of its Consultants Committee, said, "Both doctors and the NHS bear the scars of the broken pay review process.Unless these issues are fixed, the NHS will continue to haemorrhage talent and essential expertise, leaving patients without the highly skilled doctors they need to care for them."It's positive that the health secretary has agreed to talks; we now hope that he will use this extension to make a substantive offer to fix consultants' pay and the broken pay review process . . .If the government refuses to deliver a meaningful solution, our members have made it clear that they are ready to strike."The government talks came as junior doctors and Barclay continued to struggle to enter talks over their pay.Junior doctors held a 72 hour strike from 13 March and have announced a second strike of 96 hours from 11 April, citing the health secretary's refusal to make a credible pay offer. 3 41
Multicenter Phase I Trial of Ivosidenib as Maintenance Treatment Following Allogeneic Hematopoietic Cell Transplantation for <i>IDH1</i>-Mutated Acute Myeloid Leukemia
Authors: Amir T. Fathi, Haesook T. Kim, Robert J. Soiffer, Mark J. Levis, Shuli Li, Annette S. Kim, Zachariah DeFilipp, Areej El-Jawahri, Steve L. McAfee, Andrew M. Brunner, Philip C. Amrein, Alice S. Mims, Laura W. Knight, Devon Kelley, AJ S. Bottoms, Lindsey H. Perry, Jonathan L. Wahl, Jennifer Brock, Elayne Breton, Dylan M. Marchione, Vincent T. Ho, Yi-Bin Chen
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Isocitrate dehydrogenase 1 (IDH1) mutations occur in 5% to 10% of patients with acute myeloid leukemia (AML). Ivosidenib is an IDH1 inhibitor, approved for use in patients with IDH1-mutated AML. Patients and Methods: We conducted a multicenter, phase I trial of maintenance ivosidenib following allogeneic hematopoietic cell transplantation (HCT) in patients with IDH1-mutated AML. Ivosidenib was initiated between days 30 and 90 following HCT and continued for up to 12 28-day cycles. The first dose level was 500 mg daily, with level reduction to 250 mg daily, if needed, in a 3 × 3 de-escalation design. Ten additional patients would then receive the MTD or recommended phase 2 dose (RP2D). The primary endpoint was establishing the MTD or RP2D of ivosidenib. Results: Eighteen patients were enrolled, of whom 16 initiated post-HCT ivosidenib. One dose-limiting toxicity, grade(g) 3 QTc prolongation, was observed. The RP2D was established at 500 mg daily. Attributable g≥3 adverse events were uncommon, with the most common being QTc prolongation in 2 patients. Eight patients discontinued maintenance, with only one due to adverse event. Six-month cumulative incidence (CI) of gII-IV aGVHD was 6.3%, and 2-year CI of all cGVHD was 63%. Two-year CI of relapse and nonrelapse mortality (NRM) were 19% and 0%, respectively. Two-year progression-free (PFS) was 81%, and 2-year overall survival (OS) was 88%. Conclusions: Ivosidenib is safe and well-tolerated as maintenance therapy following HCT. Cumulative incidence of relapse and NRM, as well as estimations of PFS and OS, were promising in this phase I study.